Shape effect of mesoporous silica nanoparticles on cellular and in vivo functions

Summary form only given. The design of smart functional nanosystems for theranostics requires a thorough understanding of the interaction between nanoparticles (NPs) and biological systems. Recent observations suggest that physical parameters of NPs, like size, shape and surface charge, can dramatically affect the behaviors of NPs in biological systems and might, in part, determine the bioapplications of NPs. Among various factors, particle shape has been considered to play an important role in both cellular interactions with NPs and systemic distribution of NPs. However, limited information is available regarding the effects of particle shape on these biological behaviors. Mesoporous silica nanoparticles (MSNs) have recently attracted much attention in the biomedical field due to their unique characteristics, including a high BET surface area, large pore volume and uniform porosity, making them excellent candidates for development of drug delivery systems. Previous reports indicate that some nonspherical MSNs have shown some advantages in biomedical applications. In this study, different shaped monodisperse MSNs of similar particle diameter, chemical composition and surface charge but with different aspect ratios (ARs) were specially designed. The effects of these particle shapes on cellular behaviors and biological systems were studied. The results in vitro indicated that particles with larger ARs were taken up in larger amounts and had faster internalization rates. Likewise, it was also found that particles with larger ARs had a greater impact on different aspects of cellular function including cell proliferation, apoptosis, cytoskeleton formation, adhesion and migration. Furthermore, the effects of particle shape on biodistribution, clearance and biocompatibility in vivo were investigated. The organ distributions showed that MSNs were mainly present in liver, spleen and lung (>;80%) and there were obvious shape effects of particles on in vivo behaviors. Short-rod MSNs were easily trapped in liver, while more long-rod MSNs distributed in spleen. They both had a higher content in lung after PEG modification. The clearance rate of MSNs was mainly dependent on the particle shape and the type of organ. Hematology, serum biochemistry and histopathology results indicated that MSNs did not cause significant toxicity in vivo, but there was potential induction of dysfunction of biliary excretion and glomerular filtration. These findings provide strong evidence that nanostructures not only actively interact with cells, but also engage in and mediate the in vivo behaviors. Thus, the interplay between biological effects and particle shape will undoubtedly be an important aspect in investigating numerous areas of interest, including design of targeting strategies for therapeutic applications and the environmental fate of NPs.